{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T20:42:29Z","timestamp":1776372149706,"version":"3.51.2"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,3,10]],"date-time":"2016-03-10T00:00:00Z","timestamp":1457568000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100008349","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2016,5]]},"abstract":"\n Aims<\/jats:title>\n \n To assess the safety and pharmacokinetic and pharmacodynamic characteristics of\n BI<\/jats:styled-content>\n 135585, a selective 11\u03b2\u2010hydroxysteroid dehydrogenase\u20101 (11\u03b2\u2010\n HSD1<\/jats:styled-content>\n ) inhibitor, after single\u2010 and repeated\u2010dose administration.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The single\u2010dose study included open\u2010label administration of 200\u2009mg\n BI<\/jats:styled-content>\n 135585 in healthy volunteers, while in the multiple\u2010dose study, we carried out randomized, double\u2010blind administration of 5\u2013200\u2009mg\n BI<\/jats:styled-content>\n 135585 or placebo once daily over 14\u2009days in patients with type 2 diabetes (\n T2DM<\/jats:styled-content>\n ). Assessments included 11\u03b2\u2010\n HSD1<\/jats:styled-content>\n inhibition in the liver (urinary tetrahydrocortisol (\n THF<\/jats:styled-content>\n )\/tetrahydrocotisone (\n THE<\/jats:styled-content>\n ) ratio) and in subcutaneous adipose tissue (\n AT<\/jats:styled-content>\n )\n ex vivo<\/jats:italic>\n and determination of hypothalamus\u2010pituitary\u2010adrenal (\n HPA<\/jats:styled-content>\n ) axis hormone levels.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n No major safety issues occurred with\n BI<\/jats:styled-content>\n 135585 administration. The\n HPA<\/jats:styled-content>\n axis was mildly activated with slightly increased, but still normal adrenocorticotropic hormone levels, increased total urinary corticoid excretion but unchanged plasma cortisol levels. After multiple doses of 5\u2013200\u2009mg\n BI<\/jats:styled-content>\n 135585, exposure (area under the curve) increased dose\u2010proportionally and half\u2010life was 55\u201365\u2009h. The urinary\n THF<\/jats:styled-content>\n \/\n THE<\/jats:styled-content>\n ratio decreased, indicating liver 11\u03b2\u2010\n HSD1<\/jats:styled-content>\n inhibition. Median 11\u03b2\u2010\n HSD1<\/jats:styled-content>\n enzyme inhibition in the\n AT<\/jats:styled-content>\n reached 90% after a single dose of\n BI<\/jats:styled-content>\n 135585, but was low (31% or lower) after 14\u2009days of continuous treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n BI<\/jats:styled-content>\n 135585 was safe and well tolerated over 14\u2009days and can be dosed once daily. Future studies are required to clarify the therapeutic potential of\n BI<\/jats:styled-content>\n 135585 in view of its effects on 11\u03b2\u2010\n HSD1<\/jats:styled-content>\n inhibition in\n AT<\/jats:styled-content>\n after single and multiple doses. Enzyme inhibition in the\n AT<\/jats:styled-content>\n was not adequately predicted by the urinary\n THF<\/jats:styled-content>\n \/\n THE<\/jats:styled-content>\n ratio.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12635","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T09:02:51Z","timestamp":1453453371000},"page":"483-490","source":"Crossref","is-referenced-by-count":33,"title":["Safety, pharmacokinetics and pharmacodynamics of\n BI<\/scp>\n 135585, a selective 11\u03b2\u2010hydroxysteroid dehydrogenase\u20101 (\n HSD1<\/scp>\n ) inhibitor in humans: liver and adipose tissue 11\u03b2\u2010\n HSD1<\/scp>\n inhibition after acute and multiple administrations over 2\u2009weeks"],"prefix":"10.1111","volume":"18","author":[{"given":"S.","family":"Freude","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG Ingelheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Heise","sequence":"additional","affiliation":[{"name":"Profil Neuss Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.\u2010J.","family":"Woerle","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG Ingelheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Jungnik","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG Biberach Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Rauch","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG Biberach Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Sch\u00f6lch","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG Biberach Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Huang","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc. Ridgefield CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U.","family":"Graefe\u2010Mody","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co. KG Ingelheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0370"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.09.024"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/beem.2000.0119"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1254134"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2007.233"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0726"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-2315"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2009.01046.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-014-3228-6"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0957"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1019"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1996.00853.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12317"},{"key":"e_1_2_7_15_1","first-page":"A319","article-title":"Pharmacodynamic effects of AZD4017, a selective 11beta\u2010HSD1 inhibitor, in liver and adipose tissue","volume":"60","author":"Sj\u00f6strand M","year":"2011","journal-title":"Diabetes"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1912"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.10.053"},{"key":"e_1_2_7_18_1","unstructured":"WilliamsWV HuberR LevyRet\u2009al. Endocrine homeostasis with inhibition of tissue\u2010specific cortisone reductase activity in healthy volunteers and obese insulin resistant subjects following oral INCB13739 11\u00dfHSD1 inhibitor therapy.Diabetes 2007; 56 (Suppl.1): A572."},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010374470"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2010.01305.x"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.12635","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.12635","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.12635","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:24:05Z","timestamp":1761873845000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.12635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,10]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1111\/dom.12635"],"URL":"https:\/\/doi.org\/10.1111\/dom.12635","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,10]]}}}